Overview

Neuromotor control

In skeletal muscles, there are important interactions between motor neurons and the muscle fibers they innervate. For example, a motor neuron exerts a direct trophic influence over contractile protein expression and enzymatic properties of muscle fibers. In addition, muscle fibers adapt to alterations in activity of motor neurons by either increasing or decreasing their metabolic capacities. This metabolic plasticity is the basis for skeletal muscle adaptations to exercise or inactivity. The functional link between motor neurons and muscle fibers is the neuromuscular junction, which also displays considerable remodeling in response to altered use. We are also examining plasticity in neuromotor control associated with postnatal development. The pattern of skeletal muscle innervation changes markedly during early postnatal development as do the functional demands placed on muscles. It is therefore not surprising that neuromotor control during early postnatal development is characterized by remarkable remodeling.

Contractile protein expression and muscle fiber mechanics

In skeletal, cardiac, and smooth muscle fibers, we are examining relationships between contractile protein expression and mechanical and energetic properties. In particular, we are interested in the expression of different myosin heavy chain isoforms which form cross-bridges with actin during force generation and contraction. The expression of different myosin heavy chain isoforms also responds to conditions of altered use and thereby affects the mechanical and energetic properties of muscle fibers. Calcium binding to troponin C and the regulation of cross-bridge formation is also an area of interest within our laboratory.

Intracellular calcium regulation and cxcitation-contraction coupling

Elevation of intracellular calcium in is an essential signal for many physiological processes. In skeletal, cardiac, and smooth muscle cells, elevation of intracellular calcium couples external excitation by neural or chemical factors to mechanical contraction of the fiber. We are using state-of-the-art, real-time confocal microscopy to image changes in intracellular calcium in response to stimulation.

Anesthetic effects on cardiac and smooth muscle

Almost all drugs used in the practice of anesthesiology and critical care medicine exert significant hemodynamic effects by virtue of actions on the peripheral vasculature or on the myocardium. Of great clinical concern are the concentration-dependent myocardial depressant effects of intravenous and of inhalational anesthetics. Some anesthetic actions are direct on myocardial cells, some anesthetic actions are indirect through interactions with neurohumoral mechanisms that regulate myocardial contractility. Volatile anesthetics also act to relax airway smooth muscle in a concentration-dependent fashion. We are investigating the cellular mechanisms of myocardial and smooth muscle contractile depression by drugs used in clinical anesthesia. There is evidence that anesthetics depress contractility by directly decreasing the availability of intracellular calcium and (for some anesthetics) by altering myofibrillar sensitivity to calcium.

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